Genitourinary Cancer Research Articles

Perinatal Famine Exposure and Young-Onset Cancer-Lessons from China Health and Nutrition Survey.

Background/Objectives: Perinatal exposure to malnutrition has been hypothesised to influence the development of young-onset cancer (≤50 years of age). This study aimed to determine if perinatal malnutrition in individuals exposed to the Great Famine of China increased their risk of developing young-onset cancer compared to other individuals born prior to the famine. Subjects/Methods: This cross-sectional study involved 7272 participants from the China Health and Nutrition Survey who were classified into four groups based on birth year: participants born between 1953 and 1955 (before the famine) were designated as the pre-famine group (unexposed); the remainder formed perinatal exposure groups comprised of those exposed during the famine (1959-1961), those exposed in the early post-famine period (1962-1964), and those exposed in the late post-famine period (1965-1967). Multivariable adjusted log-binomial regression models were used to calculate the RR and 95% CI of young-onset cancer (including genitourinary cancer) across four groups. Results: Perinatal exposure to early post-famine (RR 2.08; 95%CI 1.04, 4.34; p = 0.043) and the female sex (RR 15.6, 95%CI 4.54, 60.3; p < 0.001) were noted to have a significantly increased risk of young-onset cancer. In addition, the early (RR 13.8; 95%CI 2.68, 253; p = 0.012) and late post-famine (RR 12.3; 95%CI 2.16, 231; p = 0.020) cohorts demonstrated a significantly increased risk of young-onset genitourinary cancer. The latter was accompanied by an increased risk of hypertension (RR 3.30; 95%CI 1.28, 7.87; p = 0.009). Conclusions: Perinatal exposure to famine, especially in females, was associated with a higher risk of young-onset cancer. This was particularly evident for young-onset genitourinary cancers. These findings highlight the potential long-term impact of perinatal malnutrition on young-onset carcinogenesis.

The roles of tertiary lymphoid structures in genitourinary cancers: molecular mechanisms, therapeutic strategies, and clinical applications.

The presence of tertiary lymphoid structures (TLSs) associated with distinct treatment efficacy and clinical prognosis has been identified in various cancer types. However, the mechanistic roles and clinical implications of TLSs in genitourinary (GU) cancers remain incompletely explored. Despite their potential role as predictive markers described in numerous studies, it is essential to comprehensively evaluate the characteristics of TLSs, including drivers of formation, structural foundation, cellular compositions, maturation stages, molecular features, and specific functionality to maximize their positive impacts on tumor-specific immunity. The unique contributions of these structures to cancer progression and biology have fueled interest in these structures as mediators of antitumor immunity. Emerging data are trying to explore the effects of therapeutic interventions targeting TLSs. Therefore, a better understanding of the molecular and phenotypic heterogeneity of TLSs may facilitate the development of TLSs-targeting therapeutic strategies to obtain optimal clinical benefits for GU cancers in the setting of immunotherapy. In this review, the authors focus on the phenotypic and functional heterogeneity of TLSs in cancer progression, current therapeutic interventions targeting TLSs and the clinical implications and therapeutic potential of TLSs in GU cancers.

Evidence-based clinical recommendations for hypofractionated radiotherapy: exploring efficacy and safety - Part 3. Genitourinary and gynecological cancers.

Hypofractionated radiotherapy (RT) has become a trend in the modern era, as advances in RT techniques, including intensity-modulated RT and image-guided RT, enable the precise and safe delivery of high-dose radiation. Hypofractionated RT offers convenience and can reduce the financial burden on patients by decreasing the number of fractions. Furthermore, hypofractionated RT is potentially more beneficial for tumors with a low α/β ratio compared with conventional fractionation RT. Therefore, hypofractionated RT has been investigated for various primary cancers and has gained status as a standard treatment recommended in the guidelines. In genitourinary (GU) cancer, especially prostate cancer, the efficacy, and safety of various hypofractionated dose schemes have been evaluated in numerous prospective clinical studies, establishing the standard hypofractionated RT regimen. Hypofractionated RT has also been explored for gynecological (GY) cancer, yielding relevant evidence in recent years. In this review, we aimed to summarize the representative evidence and current trends in clinical studies on hypofractionated RT for GU and GY cancers addressing several key questions. In addition, the objective is to offer suggestions for the available dose regimens for hypofractionated RT by reviewing protocols from previous clinical studies.

Integrated impact of multiple body composition parameters on overall survival in gastrointestinal or genitourinary cancers: A descriptive cohort study.

This study aimed to evaluate if combining low muscle mass with additional body composition abnormalities, such as myosteatosis or adiposity, could improve survival prediction accuracy in a large cohort of gastrointestinal and genitourinary malignancies. In total, 2015 patients with surgically-treated gastrointestinal or genitourinary cancer were retrospectively analyzed. Skeletal muscle index, skeletal muscle radiodensity, and visceral/subcutaneous adipose tissue index were determined. The primary outcome was overall survival determined by hospital records. Multivariate Cox hazard models were used to identify independent predictors for poor survival. C-statistics were assessed to quantify the prognostic capability of the models with or without incorporating body composition parameters. Survival curves were significantly demarcated by all 4 measures. Skeletal muscle radiodensity was associated with non-cancer-related deaths but not with cancer-specific survival. The survival outcome of patients with low skeletal muscle index was poor (5-year OS; 65.2%), especially when present in combination with low skeletal muscle radiodensity (5-year overall survival; 50.2%). All examined body composition parameters were independent predictors of lower overall survival. The model for predicting overall survival without incorporating body composition parameters had a c-index of 0.68 but increased to 0.71 with the inclusion of low skeletal muscle index and 0.72 when incorporating both low skeletal muscle index and low skeletal muscle radiodensity/visceral adipose tissue index/subcutaneous adipose tissue index. Patients exhibiting both low skeletal muscle index and other body composition abnormalities, particularly low skeletal muscle radiodensity, had poorer overall survival. Models incorporating multiple body composition prove valuable for mortality prediction in oncology settings.

In Search of Variables Affecting Mental Adjustment and Acceptance of Cancer among Urological Patients.

Background/Objectives: Genitourinary cancers are now considered a major problem in modern medicine. In urological oncology, the most frequently occurring diseases are prostate, bladder and renal cancer. Any cancer has a profound effect on the life of a patient. Therefore, disease acceptance and mental adjustment to the condition are the key elements in coping with cancer. Aim: The main aim of the study was the determination of the level of acceptance of illness and mental adjustment to cancer in urological patients undergoing surgical treatment and the assessment of the effect of mental adjustment on disease acceptance. Material and Methods: The study group comprised 150 patients treated at the Department of Urology and Urological Oncology at the Independent Public Clinical Hospital No 2 in Szczecin. The study made use of the diagnostic survey method with the original questionnaire and standardized research tools: Acceptance of Illness Scale (AIS) and Mental Adjustment to Cancer Scale (Mini-MAC). Results: The analysis of mental adjustment to cancer according to Mini-MAC revealed that the respondents most frequently adopted the fighting spirit strategy (M; 22.22). Slightly less frequently adopted strategies were positive re-evaluation (M; 21.28) and anxious preoccupation (M; 17.07). The least frequently adopted strategy was the helplessness-hopelessness strategy (M; 13.14). The analysis of data showed a statistically significant negative correlation (r = -0.245; p = 0.003) between disease acceptance according to AIS and age. The data analysis revealed a statistically significant positive correlation with helplessness-hopelessness and destructive style (p < 0.05). Conclusions: Mental adjustment to cancer was found to affect the acceptance of illness. When providing comprehensive care to cancer patients, it is equally crucial to consider the physical as well as mental health aspect, taking into account the aforementioned factors which affect both acceptance as well as adjustment to disease.

Safety and Effectiveness of Irreversible Electroporation in Lymph Node Metastases

PurposeDemonstrating the safety and efficacy of percutaneous irreversible electroporation (IRE) for the treatment of lymph node metastases.Materials and MethodsAn IRB-approved, single-center retrospective review was performed on patients with lymph node metastases gastrointestinal, and genitourinary primary cancers. Primary objective safety was evaluated by assessing complications graded according to the Clavien-Dindo Classification, and efficacy was determined by tumor response on follow-up imaging and local progression-free survival (LPFS). Secondary outcome measures were technical success (complete ablation with an adequate ablative margin > 5 mm), length of hospital stay and distant progression-free survival (DPFS).ResultsNineteen patients underwent percutaneous IRE between June 2018 and February 2023 for lymph node metastases, close to critical structures, such as vasculature, bowel, or nerves. The technical success was achieved in all cases. Complications occurred in four patients (21.1%), including two self-limiting grade 1 hematomas, a grade 1 abdominal pain, and grade 2 nerve pain treated with medication. Seventeen patients were hospitalized overnight, one patient stayed two nights and another patient stayed fourteen nights. Median follow-up was 25.5 months. Median time to local progression was 24.1 months (95% CI: 0–52.8) with 1-, 2-, and 5-year LPFS of 57.9%, 57.9% and 20.7%, respectively. Median time to distant progression was 4.3 months (95% CI: 0.3–8.3) with 1-, 2-, and 5-year DPFS of 31.6%, 13.2% and 13.2%, respectively.ConclusionIRE is a safe and effective minimally-invasive treatment for lymph node metastases in locations, where temperature dependent ablation may be contraindicated. Care should be taken when employing IRE near nerves.Graphical

Risks of adverse obstetric outcomes among female survivors of adolescent and young adult cancer in England (TYACSS): a population-based, retrospective cohort study

There are limited data on the risks of obstetric complications among survivors of adolescent and young adult cancer with most previous studies only reporting risks for all types of cancers combined. The aim of this study was to quantify deficits in birth rates and risks of obstetric complications for female survivors of 17 specific types of adolescent and young adult cancer. The Teenage and Young Adult Cancer Survivor Study (TYACSS)-a retrospective, population-based cohort of 200 945 5-year survivors of cancer diagnosed at age 15-39 years from England and Wales-was linked to the English Hospital Episode Statistics (HES) database from April 1, 1997, to March 31, 2022. The cohort included 17 different types of adolescent and young adult cancers. We ascertained 27 specific obstetric complications through HES among 96 947 women in the TYACSS cohort. Observed and expected numbers for births and obstetric complications were compared between the study cohort and the general population of England to identify survivors of adolescent and young adult cancer at a heighted risk of birth deficits and obstetric complications relative to the general population. Between April 1, 1997, and March 31, 2022, 21 437 births were observed among 13 886 female survivors of adolescent and young adult cancer from England, which was lower than expected (observed-to-expected ratio: 0·68, 95% CI 0·67-0·69). Other survivors of genitourinary, cervical, and breast cancer had under 50% of expected births. Focusing on more common (observed ≥100) obstetric complications that were at least moderately in excess (observed-to-expected ratio ≥1·25), survivors of cervical cancer were at risk of malpresentation of fetus, obstructed labour, amniotic fluid and membranes disorders, premature rupture of membranes, preterm birth, placental disorders including placenta praevia, and antepartum haemorrhage. Survivors of leukaemia were at risk of preterm delivery, obstructed labour, postpartum haemorrhage, and retained placenta. Survivors of all other specific cancers had no more than two obstetric complications that exceeded an observed-to-expected ratio of 1·25 or greater. Survivors of cervical cancer and leukaemia are at risk of several serious obstetric complications; therefore, any pregnancy should be considered high-risk and would benefit from obstetrician-led antenatal care. Despite observing deficits in birth rates across all 17 different types of adolescent and young adult cancer, we provide reassurance for almost all survivors of adolescent and young adult cancer concerning their risk of almost all obstetric complications. Our results provide evidence for the development of clinical guidelines relating to counselling and surveillance of obstetrical risk for female survivors of adolescent and young adult cancer. Children with Cancer UK, The Brain Tumour Charity, and Academy of Medical Sciences.

Acute kidney injury in cancer patients receiving anti-vascular endothelial growth factor monoclonal antibody vs. immune checkpoint inhibitors: a retrospective real-world study

BackgroundAnti-vascular endothelial growth factor monoclonal antibody (anti-VEGF) or immune checkpoint inhibitors (ICIs) combined with chemotherapy are commonly administered to cancer patients. Although cancer patients receiving anti-VEGF or ICIs have been reported to experience an increased risk of acute kidney injury (AKI), comparative studies on the AKI incidence have not been evaluated.MethodsCancer patients receiving anti-VEGF or ICIs were retrospectively selected from the hospital information system of the First Affiliated Hospital of Wenzhou Medical University between Jan, 2020 and Dec, 2022 and were divided into two groups according to the treatment regimen: anti-VEGF group and ICIs group. The baseline characteristics were propensity-score matched. The primary outcome was sustained AKI. A comparison of cumulative incidence of sustained AKI was performed by Kaplan-Meier curves and log-rank test. Risks for outcomes were assessed using Cox proportional regression.ResultsA total of 1581 cancer patients receiving anti-VEGF (n = 696) or ICIs (n = 885) were included in the primary analysis. The ICIs group had a higher cumulative incidence of sustained AKI within one year than the anti-VEGF group (26.8% vs. 17.8%, P < 0.001). Among 1392 propensity score matched patients, ICIs therapy (n = 696) was associated with an increased risk of sustained AKI events in the entire population (HR 2.0; 95%CI 1.3 to 2.5; P = 0.001) and especially in those with genitourinary cancer (HR 4.2; 95%CI 1.3 to 13.2; P = 0.015). Baseline serum albumin level (> 35 g/l) was an important risk factor for a lower incidence of sustained AKI in the anti-VEGF group (HR 0.5; 95%CI 0.3 to 0.9; P = 0.027) and the ICIs group (HR 0.3; 95%CI 0.2 to 0.5; P < 0.001).ConclusionsAmong cancer patients in this real-world study, treatment with ICIs increased incidence of sustained AKI in one year. Baseline serum albumin level was an important risk factor for sustained AKI. The risk factors for sustained AKI differed between the anti-VEGF group and the ICIs group.Trial RegistrationThe study has been registered at ClinicalTrials.gov (NCT06119347) on 11/06/2023.

The JAK-STAT signaling-related signature serves as a prognostic and predictive biomarker for renal cell carcinoma immunotherapy

Renal cell carcinoma (RCC) represents a significant portion of genitourinary cancers, marked by challenging prognosis and high metastasis rates. Immunotherapy has been applied in managing advanced renal cell carcinoma, but the therapeutic outcomes are unsatisfactory. In this study, we order to construct a Janus kinase/signal transduction and activator transcriptional (JAK/STAT)-related signature linked to kidney patient outcomes for better predicting the efficacy to immune checkpoint inhibitors (ICIs) and to provide guidance for effective combination therapy. We screened 25 differentially expressed genes (DEGs) that exhibited high expression in RCC samples and were enriched in the JAK-STAT signaling pathway. Among these genes, 11 key genes were identified and correlated with the expectation of Kidney Clear Cell Carcinoma (KIRC) patients and all these genes was significantly elevated in RCC tumor tissues and cancer cells compared to para-cancer tissues and normal renal cells. Utilizing these 11 genes, we divided RCC patients into high-risk and low-risk groups. We found a clear correlation between the clinicopathologic factors of KIRC patients and the JAK-STAT-related risk score. And the IHC results shown that the JAK3 and STAT4 expression of tumor was significantly higher than normal tissue in RCC patients, the level of JAK3 and STAT4 was positively related to the T stage of RCC patients. In addition, high-risk patients had a poorer prognosis and greater protumor immune cell infiltration, and benefitted less from immunotherapy than did low-risk patients. Furthermore, the JAK-STAT-related risk score can predict disease-free survival (DFS) in RCC patients according to the nomogram, which constructed in combination with other clinical features such as age, TNM-staging and stage. Our study demonstrated the JAK-STAT signaling pathway’s important regulatory function in RCC tumor immunity. This insight not only enhances our ability to accurately predict the survival rate of RCC patients, but also underscores a potential therapeutic alternative for RCC, involving the combined targeting of the JAK-STAT pathway and immune checkpoints.

Multimorbidity and the risk of malnutrition, frailty and sarcopenia in adults with cancer in the UK Biobank.

Malnutrition, sarcopenia and frailty are distinct, albeit interrelated, conditions associated with adverse outcomes in adults with cancer, but whether they relate to multimorbidity, which affects up to 90% of people with cancer, is unknown. This study investigated the relationship between multimorbidity with malnutrition, sarcopenia and frailty in adults with cancer from the UK Biobank. This was a cross-sectional study including 4122 adults with cancer (mean [SD] age 59.8 [7.1] years, 50.7% female). Malnutrition was determined using the Global Leadership Initiative on Malnutrition criteria. Probable sarcopenia and sarcopenia were defined using the European Working Group on Sarcopenia in Older People 2 criteria. (Pre-)frailty was determined using the Fried frailty criteria. Multimorbidity was defined as ≥2 long-term conditions with and without the cancer diagnosis included. Logistic regression models were fitted to estimate the odds ratios (ORs) of malnutrition, sarcopenia and frailty according to the presence of multimorbidity. Genitourinary (28.9%) and breast (26.1%) cancers were the most common cancer diagnoses. The prevalence of malnutrition, (probable-)sarcopenia and (pre-)frailty was 11.1%, 6.9% and 51.2%, respectively. Of the 11.1% of participants with malnutrition, the majority (9%) also had (pre-)frailty, and 1.1% also had (probable-)sarcopenia. Of the 51.2% of participants with (pre-)frailty, 6.8% also had (probable-)sarcopenia. No participants had (probable-)sarcopenia alone, and 1.1% had malnutrition, (probable-)sarcopenia plus (pre-)frailty. In total, 33% and 65% of participants had multimorbidity, including and excluding the cancer diagnosis, respectively. The most common long-term conditions, excluding the cancer diagnosis, were hypertension (32.5%), painful conditions such as osteoarthritis or sciatica (17.6%) and asthma (10.4%). Overall, 80% of malnourished, 74% of (probable-)sarcopenia and 71.5% of (pre-)frail participants had multimorbidity. Participants with multimorbidity, including the cancer diagnosis, had higher odds of malnutrition (OR 1.72 [95% confidence interval, CI, 1.31-2.30; P<0.0005]) and (pre-)frailty (OR 1.43 [95% CI 1.24-1.68; P<0.0005]). The odds increased further in people with ≥2 long-term conditions in addition to their cancer diagnosis (malnutrition, OR 2.41 [95% CI 1.85-3.14; P<0.0005]; (pre-)frailty, OR 2.03 [95% CI 1.73-2.38; P<0.0005]). There was little evidence of an association of multimorbidity with sarcopenia. In adults with cancer, multimorbidity was associated with increased odds of having malnutrition and (pre-)frailty but not (probable-)sarcopenia. This highlights that multimorbidity should be considered a risk factor for these conditions and evaluated during nutrition and functional screening and assessment to support risk stratification within clinical practice.

Circulating Tumor DNA in Genitourinary Cancers: Detection, Prognostics, and Therapeutic Implications.

CtDNA is emerging as a non-invasive clinical detection method for several cancers, including genitourinary (GU) cancers such as prostate cancer, bladder cancer, and renal cell carcinoma (RCC). CtDNA assays have shown promise in early detection of GU cancers, providing prognostic information, assessing real-time treatment response, and detecting residual disease and relapse. The ease of obtaining a "liquid biopsy" from blood or urine in GU cancers enhances its potential to be used as a biomarker. Interrogating these "liquid biopsies" for ctDNA can then be used to detect common cancer mutations, novel genomic alterations, or epigenetic modifications. CtDNA has undergone investigation in numerous clinical trials, which could address clinical needs in GU cancers, for instance, earlier detection in RCC, therapeutic response prediction in castration-resistant prostate cancer, and monitoring for recurrence in bladder cancers. The utilization of liquid biopsy for ctDNA analysis provides a promising method of advancing precision medicine within the field of GU cancers.

Trends in genitourinary cancer mortality in the United States: analysis of the CDC-WONDER database 1999-2020.

Sociodemographic disparities in genitourinary cancer-related mortality have been insufficiently studied, particularly across multiple cancer types. This study aimed to investigate gender, racial, and geographic disparities in mortality rates for the most common genitourinary cancers in the United States. Mortality data for prostate, bladder, kidney, and testicular cancers were obtained from the Centers for Disease Control and Prevention (CDC) WONDER database between 1999 and 2020. Age-adjusted mortality rates (AAMRs) were analyzed by year, gender, race, urban-rural status, and geographic region using a significance level of p < 0.05. Overall, AAMRs for prostate, bladder, and kidney cancer declined significantly, while testicular cancer-related mortality remained stable. Bladder and kidney cancer AAMRs were 3-4 times higher in males than females. Prostate cancer mortality was highest in black individuals/African Americans and began increasing after 2015. Bladder cancer mortality decreased significantly in White individuals, Black individuals, African Americans, and Asians/Pacific Islanders but remained stable in American Indian/Alaska Natives. Kidney cancer-related mortality was highest in White individuals but declined significantly in other races. Testicular cancer mortality increased significantly in White individuals but remained stable in Black individuals and African Americans. Genitourinary cancer mortality decreased in metropolitan areas but either increased (bladder and testicular cancer) or remained stable (kidney cancer) in non-metropolitan areas. Prostate and kidney cancer mortality was highest in the Midwest, bladder cancer in the South, and testicular cancer in the West. Significant sociodemographic disparities exist in the mortality trends of genitourinary cancers in the United States. These findings highlight the need for targeted interventions and further research to address these disparities and improve outcomes for all populations affected by genitourinary cancers.

Preoperative COVID-19 and Postoperative Mortality in Cancer Surgery: A South Korean Nationwide Study

BackgroundWe evaluated the impact of preoperative COVID-19 on early postoperative mortality in patients undergoing time-sensitive cancer surgery.MethodsThis retrospective, nationwide cohort study included adult patients who underwent various cancer (thyroid, breast, stomach, colorectal, hepatobiliary, genitourinary, lung, and multiple cancer) surgeries under general anesthesia in South Korea in 2022. Patients were grouped according to the duration from the date of COVID-19 confirmation to the date of surgery (0–2 weeks, 3–4 weeks, 5–6 weeks, and ≥7 weeks). Patients without preoperative COVID-19 also were included. Multivariable logistic regression analysis with Firth correction was performed to investigate the association between preoperative COVID-19 and 30-day and 90-day postoperative mortality. The covariates encompassed sociodemographic factors, the type of surgery, and vaccination status in addition to the aforementioned groups.ResultsOf the 99,555 patients analyzed, 30,933 (31.1%) were preoperatively diagnosed with COVID-19. Thirty-day mortality was increased in those who underwent surgery within 0–2 weeks after diagnosis of COVID-19 (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.02–2.12; P = 0.038); beyond 2 weeks, there was no significant increase in mortality. A similar pattern was observed for 90-day mortality. Full vaccination against COVID-19 was associated with reduced 30-day (OR 0.38; 95% CI 0.29–0.50; P < 0.001) and 90-day (OR 0.39; 95% CI 0.33–0.46; P < 0.001) mortality.ConclusionsCancer surgery within 2 weeks of COVID-19 diagnosis was associated with increased early postoperative mortality. These findings support current guidelines that recommend postponing elective surgery for at least 2 weeks after the diagnosis of COVID-19.

Germline Pathogenic Variants Identified in Patients With Genitourinary Malignancies Undergoing Universal Testing: A Multisite Single-Institution Prospective Study.

This study aimed to investigate the prevalence of pathogenic germline variants (PGVs) in hereditary cancer genes utilizing a universal testing approach and to determine the rate of PGVs that would have been missed based on National Comprehensive Cancer Network (NCCN) guidelines in genitourinary (GU) malignancies. A multisite, single-institution prospective germline genetic test (GGT) was universally offered to patients with new or active diagnoses of GU malignancies (prostate, bladder, and renal) from April 2018 to March 2020 at Mayo Clinic sites. Participants were offered GGT using a next-generation sequencing panel of > 80 genes. Demographic, tumor characteristics, and genetic results were evaluated. NCCN GU cancer guidelines were used to identify whether patients had incremental findings, defined as PGV-positive patients who would not have received testing based on NCCN guidelines. Of 3095 individuals enrolled in the study, 601 patients had GU cancer (prostate = 358, bladder = 106, and renal = 137). The mean enrollment age was 67 years (SD 9.1), 89% were male, and 86% of patients were non-Hispanic White. PGVs were identified in 82 (14%) of all GU patients. PGV prevalence breakdown by cancer type was: 14% prostate, 14% bladder, and 13% renal cancer. Nearly one-third of identified PGVs were high penetrance, and the majority of these (67%) were clinically actionable. Incremental PGVs were identified in 28 (57%) prostate, 15 (100%) bladder, and 14 (78%) renal cancer patients. Of the 82 patients with PGV findings, 29 (35%) had at least 1 relative undergo cascade testing for the familial variant(s) identified. More than 1 in 8 patients with GU malignancies were found to carry a PGV, with 67% of patients with high-penetrance PGVs undergoing clinically actionable changes. The majority of these PGVs would not have been identified based on current testing criteria. These findings support universal GGT for GU malignancies and underscore its potential to enhance risk assessment and guide precision interventions in urologic oncology.

Current Status and Challenges in Rare Genitourinary Cancer Research and Future Directions.

In contemporary urological practice, managing rare genitourinary (GU) malignancies presents significant challenges, necessitating a comprehensive understanding of their unique characteristics and tailored treatment approaches. Rare GU malignancies, whether per se, variants of common histologies, or common tumors in uncommon locations, often lack widely available clinical guidelines. Consequently, treatment decisions are frequently based on empirical evidence, risking suboptimal outcomes. However, recent advances in molecular profiling, targeted therapies, and immunotherapy offer promising avenues for improving management strategies and patient outcomes. This review provides a comprehensive overview of some rare GU malignancies encountered in clinical practice, including their distinct pathological features, current management approaches, and ongoing research directions. Understanding the complexities of these rare tumors and implementing multidisciplinary treatment strategies are essential for optimizing patient care and improving survival outcomes.

Impact of race and ethnicity on financial toxicity in patients with genitourinary cancers.

11077 Background: Genitourinary (GU) cancers contribute substantially to the cost of healthcare in the United States (US). While advancements in cancer treatment have improved patient outcomes, disparities in healthcare costs persist, exacerbating the financial burden on vulnerable populations. We sought to investigate the disparities in costs of inpatient hospitalizations among patients with GU cancers in the US. Methods: Eligible adult GU cases from the Medical Expenditure Panel Survey (2019–2021) were included in this study. ICD-10 CM codes were utilized to identify renal cell, prostate, urothelial, testicular, and penile cancers. In addition to the total hospital inpatient (IP) facility expenditure, questions about ability to pay for healthcare were included in the analysis after accounting for the complex survey design and sampling weights. Results: The study included a weighted sample size of 9,061,181 (wt SE = 538,502) GU cases in the US between 2019 and 2021. The mean (95% CI) age of the sample was 71.6 (70.7, 72.5) years. The sample consisted of 7.9% Hispanics, 74.8% non-Hispanic White (NHW), 13.8% non-Hispanic Black (NHB), and 3.5% Asian or other races (NHA). In 2021, NHB participants reported the lowest annual family income of $51742 (18932, 106185), followed by Hispanics with $65233 (24314, 95859), and NHW with 82035 (36298, 158863). A greater proportion of the elderly NHW population was insured compared to NHB and Hispanics (44.9% vs. 32.5% vs. 19.5%), respectively. Of note, NHB patients had worse self-perceived physical and mental health compared to NHW and Hispanics, with 18.1% reporting fair or poor physical and mental health (vs. 8.1% and 14.3%, respectively). NHB participants reported higher rates of familial financial hardship (2019: 10.2% vs. 3.6%; 2020: 6.2% vs. 3.5%; 2021: 7.1% vs. 3.3%) or not being able to afford medical care (2019: 7.2% vs. 2.1%; 2020: 2.5% vs. 0.6%; 2021: 1.9% vs. 1.7%) when compared to NHW. Overall, mean total hospital IP facility expenses were: Hispanics = $2873.30 (1434.49, 4312.12); NHW = $4213.81 (3241.05, 5186.56); and NHB = $5199.99 (2842.93, 7557.05). After accounting for sample weights, gender, family income, age, insurance status, and survey year, Poisson regression analysis showed significant differences between different racial groups. Hispanics were less likely (𝛽=-0.48; p&lt;0.0001), while NHB (𝛽=0.152; p&lt;0.0001) and NHA (𝛽=0.48; p&lt;0.0001) were more likely to spend for an IP hospitalization when compared to NHW (ref.). Conclusions: Our data revealed racial disparities in the costs of inpatient hospitalizations, highlighting potential financial toxicity among patients with GU cancers. Additional investigation is warranted to elucidate factors contributing to these inequities, aiming to optimize cancer management and alleviate financial burdens. Addressing these disparities is crucial to prioritize equitable healthcare access and promote systemic change.

Clinical Applications of the Gut Microbiome in Genitourinary Cancers.

Recently recognized as one of the hallmarks of cancer, the microbiome consists of symbiotic microorganisms that play pivotal roles in carcinogenesis, the tumor microenvironment, and responses to therapy. With recent advances in microbiome metagenomic sequencing, a growing body of work has demonstrated that changes in gut microbiome composition are associated with differential responses to immune checkpoint inhibitors (ICIs) because of alterations in cytokine signaling and cytotoxic T-cell recruitment. Therefore, strategies to shape the gut microbiome into a more favorable, immunogenic profile may lead to improved responses with ICIs. Immunotherapy is commonly used in genitourinary (GU) cancers such as renal cell carcinoma, urothelial cancer, and to a limited extent, prostate cancer. However, a subset of patients do not derive clinical benefit with ICIs. Gut microbiome-based interventions are of particular interest given the potential to boost responses to ICIs in preclinical and early-phase prospective studies. Novel approaches using probiotic therapy (live bacterial supplementation) and fecal microbiota transplantation in patients with GU cancers are currently under investigation.

Linking in with advice and supports for men impacted by metastatic cancer: The LIAM Mc trial (NCT05946993).

TPS1646 Background: Multidisciplinary supportive care interventions are key to preventing and managing adverse effects of cancer and its treatment for patients, reducing symptom and psychological burdens and enhancing quality of life (QoL). However, the optimal composition of these interventions for men with genitourinary (GU) cancers is poorly understood. The LIAM Mc Trial is an enhanced supportive care programme, funded by the Irish Cancer Society and designed with the input of patient representatives who highlighted the unmet needs of cancer survivors. An important aspect of the trial is to demonstrate how to improve the survivorship supports and services for underserved communities of men who experience disparities in cancer incidence, prognosis, outcome and QoL, and have not traditionally been the focus of such initiatives. Methods: Using an embedded mixed-method process evaluation this prospective trial aims to assess the feasibility and impact of a holistic 12-week survivorship programme amongst men with advanced GU cancers at an Irish Cancer Centre. The programme involves twice-weekly sessions with input from a dedicated physiotherapist, dietitian, and nurse specialist, along with education sessions from medical social worker and psycho-oncology specialists, and programme oversight provided by medical oncologists. Outcomes are measured at three timepoints; pre-intervention, immediately post-intervention and at 6 months post intervention, and will include EORTC QoL; muscle strength; body composition through bioelectrical impedance analysis and ultrasound; diet quality; cancer related symptom control; cancer related fatigue scores; feasibility outcomes, qualitative interviews and a process evaluation. Any man with a locally advanced or metastatic GU cancer who has recently completed a course of treatment or is stable on active anti-cancer treatment is eligible for the programme. Over the two-year study period the sample size target is 72 participants. The primary endpoint of the study is to evaluate the feasibility of introducing an enhanced supportive care programme as part of routine management for male cancer patients with metastatic disease. Acceptability, satisfaction with the programme and QoL changes are key secondary endpoints. Barriers to participation are also a key outcome under investigation. The study was activated in May 2023 with the first participants enrolled in June 2023. To date 17 men have enrolled with accrual completion anticipated in June 2025. Clinical trial information: NCT05946993 .

Clustering analysis for predicting racial disparities in genitourinary cancer–related financial burden.

e13612 Background: Healthcare costs in the United States (US) are significantly impacted by genitourinary (GU) cancers. Prostate cancer treatment alone cost the US more than $22 billion in 2020. We sought to utilize machine learning (ML)-based classification to investigate differences in the total cost of healthcare expenditure among patients with GU cancer in the US. Methods: The study included eligible adult GU cases from the 2019–2021 Medical Expenditure Panel Survey. Renal cell, prostate, urothelial, testicular, and penile cancers were identified using ICD-10 CM codes. Patients were clustered using demographic information such as age, race, sex, marital status, highest degree, insurance status, perceived health status, and perceived mental health status. The analysis accounted for the complex survey design and sampling weights. The cluster groups were taken into account when conducting descriptive and regression analyses. GU cancer cases were divided into low-, medium-, and high-risk healthcare expenditure clusters. Results: The study included a representative sample of 9,061,181 cases of GU cancer in the US between 2019 and 2021. The average age of the sample was 71.6 years (95% CI: 70.7, 72.5). There were 7.9% Hispanic (Hisp), 74.8% non-Hispanic White (NHW), 13.8% non-Hispanic Black (NHB), and 3.5% individuals from Asian or other races. Overall, the mean total healthcare expenditures within low-, med-, and high-risk clusters were $17974 (13816, 22133), $20496 (13100, 27893), and $30512 (21389, 39635), respectively. Regression analysis showed that, after adjusting for sampling weight, cluster, gender, family income, age, insurance status, and survey year, the mean total expenditure was higher by $11209.70 and $13100.81 in med- and high-risk clusters when compared to the low-risk cluster (ref.). Within each race or ethnicity, the proportion of Hisp or NHB individuals was higher in med- and high-risk clusters. Med- and high-risk clusters were more likely to contain people with cognitive impairments, poor health status, and financial difficulties in their families. Conclusions: We used an unsupervised clustering algorithm that can distinguish between GU cases with high and low expenditure based solely on sociodemographic variables. We demonstrate that our findings were consistent for all three data cohorts. This approach can predict the disparity in utilization in any insured population. [Table: see text]

Pembrolizumab-induced myocarditis: A systematic review of case reports.

e14605 Background: Immune checkpoint inhibitors, such as pembrolizumab, have revolutionized cancer therapy but are associated with immune-related adverse events (irAEs), including myocarditis, which can have serious clinical consequences. This systematic review aims to comprehensively analyze case reports to better understand pembrolizumab-induced myocarditis. Methods: Using keywords of "pembrolizumab" or "Keytruda" and "myocarditis" in the PubMed/Medline, ScienceDirect and clinicaltrials.gov databases and manual searches on Google Scholar, we reviewed all cases reported up to the year 2023. In total, 296 studies received primary screening. Duplicated articles and those meeting the exclusion criteria (not myocarditis, not human, not English, trials done in vitro, combination immunotherapies) were excluded. Review articles, retrospective studies, systematic reviews, and meta-analyses were also excluded. Finally, 45 studies matching the inclusion criteria were included (total of 46 patients). Data on patient demographics, clinical presentation, diagnostic criteria, management strategies, and outcomes were extracted and analyzed. Results: In the included 46 patients, the mean age was 65.5 years, with a slight male predominance (56.5%). Predominant cancer types included lung cancer (30.4%), thymoma (15.2%), melanoma (13.0%), and genitourinary cancers (13.0%). 45.7% of patients developed myocarditis after their first cycle of Pembrolizumab while 41.3% developed myocarditis after two cycles. 47.8% of patients presented with dyspnea, 23.9% with fatigue, 10.9% with chest pain, while 13% of the patients were asymptomatic and were subsequently diagnosed with myocarditis while presenting with other immune-related adverse events. Troponin levels were assessed in 45 individuals, with only 2.2% (one patient) having normal levels. ECG changes included ST segment elevation in 21.7%, conduction abnormalities (RBBB 15.2%, LBBB 6.5%, AV block 26.1%, and one unspecified conduction abnormality) in 50%, and arrhythmias in 37% of cases. Treatment included steroids for all, with varying outcomes. Four patients each received one of the following treatments: batacept, ruxolitinib, alemtuzumab, and methotrexate. All four of these patients showed improvement. Two patients received infliximab (4.3%) and both of them died. Outcomes revealed 34.8% mortality, 63.0% improvement, and 2.2% deterioration, including one sudden cardiac death 35 days post-discharge. Conclusions: Pembrolizumab-induced myocarditis is a rare but potentially life-threatening irAE. This systematic review provides a comprehensive overview of the clinical characteristics, diagnostic challenges, treatment approaches, and outcomes of this condition. Further research is needed to elucidate the underlying mechanisms and identify risk factors for pembrolizumab-induced myocarditis, enabling early detection and prevention strategies.